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Engineering Carbon-carbon Bond Forming Enzymes from Plants for Applications in Industrial Biotechnology

Project Description

The synthesis of biologically active pharmaceutical compounds requires that chemical intermediates are synthesised in a very specific way, giving only one of two possible isomeric forms, as the unwanted form may be inactive or even toxic. One important class of reaction in pharmaceutical synthesis is the formation of carbon-carbon bonds. It is a significant challenge to form these bonds to give single compound isomers, and increasingly both academics and industrialists are turning to enzymes – nature’s biological catalysts - as an efficient way of making these compounds. Not only do enzymes naturally possess the selectivity to make single isomers, they are also attractive from the perspective of sustainable, green chemistry, as they work at ambient temperature and pressure, do not require toxic chemical reagents, and generate lower hazard waste than non-biological catalysts.

Many kinds of enzyme have been used to make carbon-carbon bonds, but an emerging class of enzymes – 2-OG dependent dioxygenases (2-ODDs) - have recently being described, which offer new and improved ways to catalyse these important reactions. In this project we propose to develop 2-ODD technology, with a view to offering valuable new enzyme catalysts for industry. We will use X-ray crystallography to determine the molecular structure of these enzymes, and this will allow us to make conclusions about how they work at a molecular level. We can then use protein engineering techniques to make the enzymes work better on the reactions of interest, but also expand their applicability so that they work on new reactions that are not catalysed by the natural enzymes. We can also use the structural information to improve the way that the enzymes will perform under industrial process conditions, resulting in important new information on a largely unexplored group of enzymes, and valuable catalysts for the production of important industrial synthetic intermediates.

This prestigious BBSRC funded Doctoral Training Partnership (DTP) brings together the very best molecular, chemical and cellular bioscience research across the White Rose Consortium of Universities (Leeds, Sheffield and York), which maps on to the research themes of the BBSRC. Students will benefit from a regional PhD training programme that has interdisciplinary collaboration at its core. The aim is to enable students to develop a range of research skills in biological and biochemical areas as well as equip them with core mathematical, data analysis and generic professional skills that are necessary for bioscience research in the coming decades. At York, the White Rose Partnership brings together researchers from the Departments of Biology and Chemistry.

Additionally, all Chemistry research students have access to our innovative Doctoral Training in Chemistry (iDTC): cohort-based training to support the development of scientific, transferable and employability skills.

Panel interviews will take place at the University of York on 6 February 2019

The Department of Chemistry holds an Athena SWAN Gold Award and is committed to supporting equality and diversity for all staff and students. The Department strives to provide a working environment which allows all staff and students to contribute fully, to flourish, and to excel:

This PhD will formally start on 1 October 2019. Induction activities will start on 30 September.

Funding Notes

Value: Studentships are fully funded by BBSRC and cover: (i) a tax-free annual stipend at the standard Research Council rate (£14,777 for 2018-2019, to be confirmed for 2019-2020 but typically increases annually in line with inflation), (ii) research costs, and (iii) tuition fees at the UK/EU rate.
Eligibility: The studentships are available to UK and EU students who meet the UK residency requirements. Students from EU countries who do not meet the residency requirements may still be eligible for a fees-only award. Further information about eligibility for Research Council UK funding can be found at the following website: View Website

Related Subjects

How good is research at University of York in Chemistry?

FTE Category A staff submitted: 47.06

Research output data provided by the Research Excellence Framework (REF)

Click here to see the results for all UK universities

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